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Background: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival., Methods: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS)., Results: Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively)., Conclusions: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

Introduction: Pasireotide (SOM230) is a somatostatin analog with high binding affinity for somatostatin receptors including sst1, 2, 3 and 5 and inhibit insulin like growth factor-1. Blocking of IGF-1 receptor (IGF-1R) in combination with cytotoxic chemotherapy has demonstrated additive or synergistic activity in pre-clinical models. This study aimed to evaluate the maximum tolerated dose (MTD) of pasireotide in combination with standard FOLFIRI (5-fluorouracil, leucovorin and irinotecan) regimen in patients with gastrointestinal malignancies., Methods: This was a phase 1, 3 + 3 design, open-label dose escalation study conducted in sequential cohorts to determine the MTD of pasireotide in combination with FOLFIRI. All patients had gastrointestinal malignancies and were previously treated. Sixteen patients enrolled in five dose cohorts at pasireotide doses of 40, 60, 80, 100 and 120 mg were evaluated for safety and tolerability of the combination., Results: The tumor types of the enrolled subjects included esophageal (n = 5), biliary tract (n = 3), colon (n = 3), gastric (n = 2), pancreatic (n = 1), anal (n = 1) and small bowel (n = 1). No dose limiting toxicities were observed. The most common adverse events related to the study treatment included hyperglycemia (81 %), neutropenia (62 %), thrombocytopenia (44 %), anorexia (44 %), dehydration (25 %) and elevated alkaline phosphatase (25 %). Two patients had partial response and 7 patients had stable disease. Plasma levels of IGF-1 and IGFBP-3 were significantly reduced after treatment with pasireotide., Discussion: Combination of pasireotide and FOLFIRI has manageable safety profile and is feasible in patients with gastrointestinal malignancies. Preliminary signals of activity were observed. Larger phase II trials are warranted.

Introduction: Cytoreduction with heated intraperitoneal chemotherapy (HIPEC) has demonstrated improved overall survival (OS) in malignant peritoneal mesothelioma (MPM). The role of repeated HIPEC for MPM is less clear., Methods: An institutional review board-approved database of MPM patients was analyzed for clinical factors and outcomes., Results: From June 2004 to March 2012, 29 patients underwent surgical treatment for mesothelioma. HIPEC was aborted in 3 and completed in 26; 8 underwent additional repeat HIPEC. The majority was male (62 %), median age 66 years. There was no significant difference in surgery duration, blood loss, or hospital-stay-duration between initial and repeat HIPEC. Cisplatin was the chemotherapy used. Complications occurred in 17 (65 %) initial and 6 (50 %) repeat HIPEC, with wound complications being most common. Reoperation was less common (4 % initial and 25 % repeat), and perioperative death was rare (4 % initial, 0 % repeat). Fourteen (54 %) initial and seven (58 %) repeat HIPEC patients received adjuvant chemotherapy. Median time from HIPEC to initiation of chemotherapy was not different between initial and repeat HIPEC (8.8 and 4.6 months, respectively, p = 0.68). Median treatment-free time (time from initial to repeat HIPEC or chemotherapy) also was not different between initial and repeat HIPEC (8.8 and 6.3 months, respectively, p = 0.92). Median OS for the cohort was 41.2 months. Patients who underwent repeat HIPEC had improved median OS (80 months) versus single HIPEC (27.2 months; p = 0.007). A lower peritoneal carcinoma index and complete cytoreduction were associated positively with OS., Conclusions: Cytoreduction and HIPEC for MPM are associated with longer OS. Patients who are candidates for repeat HIPEC may derive an even greater OS advantage.

The objective of this study is to evaluate whether a patient navigation (PN) program is effective in reducing delay in diagnostic resolution among medically underserved patients with colorectal cancer (CRC)-related abnormalities in Tampa Bay, Florida. This study involved ten primary care clinics randomized either to receive navigation or to serve as controls (five clinics per arm). Each clinic identified all subjects with CRC-related abnormalities in the year prior to the clinic beginning participation in the Moffitt Patient Navigator Research Program. Patients with CRC-related abnormalities were navigated from the time of a colorectal abnormality to diagnostic resolution. Control patients received usual care, and outcome information was obtained from medical record abstraction. Using a frailty Cox proportional hazard model, we examined the length of time between colorectal abnormality and definitive diagnosis. One hundred ninety-three patients were eligible for the study because of a CRC-related abnormality (75 navigated and 118 controls). Analysis of PN effect by two time periods of resolution (0-4 and >4 months) showed a lagged effect of PN. The adjusted time-varying PN effect on diagnostic resolution compared to the controls was marginally significant (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval = 1.02-1.29) after controlling for insurance status. The predicted aHR at 4 months was 1.2, but showed no significant effect until 12 months. For patients having an abnormal symptom of CRC, PN appeared to have a positive effect over time and sped diagnostic resolution after 4 months. However, the small sample size limits drawing a definitive conclusion regarding the positive PN effect.